alpha1,2 blockers, drugs acting on imidazoline and indirect sympathomimetics

Question 1

what are the alpha 1 agonist and uses:

Answer 1

phenylpherine, midodrine and methoxamine.

Local:
• opthalmologic use
• decongestion (phenylephrine) • mydriasis (phenylephrine) • treatment of glaucoma (apraclonidine, brimonidine)

• opthalmologic use
• decongestion (phenylephrine) • mydriasis (phenylephrine) • treatment of glaucoma (apraclonidine, brimonidine)

systemic use

• cause vasoconstriction, elevate the blood pressure
• e.g. phenyleprine, midodrine, methoxamine

Question 2

phenylpherine

Answer 2

ALpha 1 agonist.

Uses: Nasal decongestant and opthalmology (mydriasis without cycloplegia).

Question 3

methoxamine

Answer 3

alpha 1 agonist

Used for PAT

Kinetics:
IV
Prodrug-> active drug

Question 4

midodrine

Answer 4

alpha 1 agonist

orothostatic hypotension due to impaired ANS.

Question 5

what are the alpha 2 agonists and function

Answer 5

clonidine, 
guanfacine, 
guanbenz, 
methyldopa, 
apraclonidine and 
dexmedetomidine.

• reduce the sympathetic tone, decrease the blood pressure (due to the enhancement of the negative feed back of norepinephrine and/or central activation of 
2 receptors involved in blood pressure regulation)

Question 6

clonidine

Answer 6

ALpha 2 agonist

imidazoline deriv.
inhibts the sympathetic vasomotor centers by stimulating the Imidazoline receptors in the rostral ventrolateral medulla and also by acting on the alpha 2 receptor (inhibitory) in the presynpatic noradregenic nerve terminals.

Indication: Mild and moderate HTN.
• potential indications (clonidine or derivatives): • treatment of mild to moderate hypertension (mostly in acute cases)
• alcohol and opiate withdrawal; cessation of smoking;
• perianesthetic mediaction
• sedation and analgesia in intensive care, adjuvant analgesic (epidural,
intrathecal)
• diarrhea in diabetics
• ADHD
• glaucoma

Adverse effects: 
Sedation, 
dry mouth, 
bradycardia, 
orthostatic hypotension, 
sexual disturbances and depression.

Abrupt withdrawl: hypertensive crisis, must withdrawl slowly.

Question 7

guanfacine+ guanbenz

Answer 7

Alpha 2 agonist

Used for hypertension

Question 8

methyldopa

Answer 8

ALpha 2 agonist

competes with DOPA in NE synthesis and produces an end product called methylnorepinephrine which is a false transmitter (either stimulates alpha 2 receptors or blocks dopa decaboxylase.. can’t find

Inidcation:

1) HTN in pregnancy.
2) HTN generally

Side-affects: almost similar to clonidine, just also postivei coombs test and liver toxicity.

Question 9

apraclonidine and brimodine

Answer 9

ALpha 2 agonist

treatment for glucoma.

Question 10

dexmedetomidine

Answer 10

ALpha 2 agonist

Centally acts on receptors

indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care seting

Question 11

what are non selective alpha receptor agonists (although said to be alpha 2 A subunit…)

Answer 11

oxymetazoline and xylometazoline
direct acting alpha agonist
have been used as topical decongestants in the conjunctiva.
said to have high affinity to alpha2 A subunit..

Question 12

what are the mixed action adrenergic agonist and what do they do? (indirect sympathomimetic)

Answer 12

ephedrine and pseudoephedrine

both induce release of NE from the presynaptic terminals and stimulate directly the adregenic receptors (post-synaptic).
Taken orall and PENETRATE THE CNS.
LESS POTENT THAN CATECHOLAMINES AND LONGER DURATION.

Question 13

ephedine

Answer 13

high oral bioavalability, long duration of action
• penetration through the blood-brain barrier, mild stimulant
• mixed sympathomimetic mechanism of action: weak
receptor activator and releases norepinephrine
• its enantiomer is pseudoephedrine – available over-the- counter as a component of many decongestant mixtures.

• can be used as a vasoconstrictor or a bronchodilator when weak and prolonged action is needed

Question 14

indirect acting sympathomimetics- who are they and what are their char.

Answer 14

Indirectly acting sympathomimetics
• They release norepinephrine from the nerve terminals
• Rapid development of tolerance (tachyphylaxis) is
characteristic to their actions
• Tyramine, ephedrine andamphetamine belong to this
group

Question 15

amphetamine

Answer 15

• orally active compound with long duration of action
• enters the CNS very easily, releases biologic amines and causes a marked stimulant effect on mood and alertness (psychostimulant)
• euphoria leads to abuse of this drug
• decreases the appetite
• on the periphery it is an indirectly acting sympathomimetic-> increases BP by acting on alpha 1 agonists and beta stimulatory affects on the heart.
used for: ADHD, anorexian and narcolepsy
taken oral or parental.
Mediated by release of NE and blockage of the uptake of NE.

• structurally related drugs:
methylphenidate (treatment of ADHD),
pemoline,
phenmetrazine,
metamphetamine,
MDMA (ecstasy)

Question 16

tyramine

Answer 16

• It is not used as a therapeutic agent.
• It can be found in high concentration in foods (cheese,
chicken liver, smoked or pickled fish, red wine).
• It is metabolized by MAO-A in the gastroinstestinal tract,and inactivated if ingested.
like amphetamine it can enter the nerve terminal and displace stored NE.

• Cheese-effect:
Patients treated with irreversible MAO-A inhibitors must avoid foods containing
tyramine. If they don’t do that, tyramine reaches the systemic circulation, and
increases the sympathetic tone by releasing norepinephrine. It can cause
hypertensive crisis.

Question 17

MAO inhibitors

Answer 17

MAO-Inhibitors
• Irreversible non selective MAO inhibitors
• eg. tranylcypromine, pargyline
• old-fashioned antidepressive drugs, their use is not recommended because of severe side-effects (eg. cheese-effect)

• Reversible MAO-A inhibitors
• eg. moclobemid
• used for the treatment of mental depression, doesn’t cause cheese effect
• Irreversible MAO-B inhibitors
• selegiline
• used for the treatment of Parkinson’s disease
• doesn’t cause cheese effect

Question 18

reuptake inhibitors

Answer 18

• Reuptake inhibitors
• Cocaine
• local anaesthetic
• blocks NA and DA reuptake on the periphery and in the CNS, causes sympathomimetic actions,
euphoria and drug abuse

• TCA and related compounds
• eg. desipramine, amitriptyline
• used for the treatment of mental depression,
block the norepinephrine (and serotonine) reuptake
in the CNS and on the periphery
•  and M blockade may complicate their
autonomic actions; risk of cardial adverse
effects

• SNRI, SSNRI
• e.g. reboxetine, venlafaxine
• antidepressants, no receptor blockade

Question 19

imidazoline deriv

Answer 19

Moxonidine and rilmenidine
• newer imidazoline-derivatives, with clonidine-like structure
• bind more selectively to I1 receptors ?

• indication: treatment of hypertension
• sedation and dry mouth occurs less frequently than with clonidine

Question 20

drugs acting on the imidazoline receptor

Answer 20

I think clonoidine should be included here besides:
Moxonidine and rilmenidine:
newer drugs
i1 affinity&raquo_space;> alpha 2 (compared to clonidine)
used for hypertension treatment.
adverse: dry mouth and sedation.

Question 21

Tizanidine

Answer 21

ALpha 2 agonist, centrally works to cause muscle relax